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  1. Article ; Online: Immune signature of patients with cardiovascular disease – in-depth immunophenotyping predicts increased risk for a severe course of COVID-19

    Günter, Manina / Mueller, Karin Anne Lydia / Salazar, Mathew / Gekeler, Sarah / Prang, Carolin / Harm, Tobias / Gawaz, Meinrad Paul / Autenrieth, Stella E.

    medRxiv

    Abstract: Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD ... ...

    Abstract Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at hospital admission are still missing. Here, we investigated whether the severity of SARS-CoV-2 infection can be predicted by analyzing the immunophenotype in the blood of CVD patients. Approach and Results: We prospectively analyzed the peripheral blood of 94 participants, including CVD patients with acute SARS-CoV-2 infection, uninfected CVD patients, and healthy donors using a 36-color spectral flow cytometry panel. Clinical assessment included blood sampling, echocardiography, and electrocardiography. Patients were classified by their ISARIC WHO 4C-Mortality-Score on the day of admission into three subgroups of an expected mild, moderate, or severe course of COVID-19. Unsupervised data analysis revealed 40 clusters corresponding to major circulating immune cell populations. This revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4<sup>+</sup> T cells, and plasmablasts than uninfected CVD patients. In contrast, fewer dendritic cells, CD16<sup>+</sup> monocytes, innate lymphoid cells, and CD8<sup>+</sup> T cell subsets were detected in SARS-CoV-2-infected CVD patients. We identified an immune signature characterized by low frequencies of MAIT and intermediate effector CD8<sup>+</sup> T cells in combination with a high frequency of NKT cells that is predictive for CVD patients with a severe course of SARS-CoV-2 infection on hospital admission. Conclusion: Acute SARS-CoV-2 infected CVD patients revealed marked changes in abundance and phenotype of several immune cell populations associated with COVID-19 severity. Our data indicate that intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.
    Keywords covid19
    Language English
    Publishing date 2023-04-26
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.04.24.23288921
    Database COVID19

    Kategorien

  2. Article ; Online: Immune signature of patients with cardiovascular disease - in-depth immunophenotyping predicts increased risk for a severe course of COVID-19

    Guenter, Manina / Mueller, Karin Anne Lydia / Salazar, Mathew James / Gekeler, Sarah / Prang, Carolin / Harm, Tobias / Gawaz, Meinrad / Autenrieth, Stella E.

    medRxiv

    Abstract: Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD ... ...

    Abstract Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at hospital admission are still missing. Here, we investigated whether the severity of SARS-CoV-2 infection can be predicted by analyzing the immunophenotype in the blood of CVD patients. Approach and Results: We prospectively analyzed the peripheral blood of 94 participants, including CVD patients with acute SARS-CoV-2 infection, uninfected CVD patients, and healthy donors using a 36-color spectral flow cytometry panel. Clinical assessment included blood sampling, echocardiography, and electrocardiography. Patients were classified by their ISARIC WHO 4C-Mortality-Score on the day of admission into three subgroups of an expected mild, moderate, or severe course of COVID-19. Unsupervised data analysis revealed 40 clusters corresponding to major circulating immune cell populations. This revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4<sup>+</sup> T cells, and plasmablasts than uninfected CVD patients. In contrast, fewer dendritic cells, CD16<sup>+</sup> monocytes, innate lymphoid cells, and CD8<sup>+</sup> T cell subsets were detected in SARS-CoV-2-infected CVD patients. We identified an immune signature characterized by low frequencies of MAIT and intermediate effector CD8<sup>+</sup> T cells in combination with a high frequency of NKT cells that is predictive for CVD patients with a severe course of SARS-CoV-2 infection on hospital admission. Conclusion: Acute SARS-CoV-2 infected CVD patients revealed marked changes in abundance and phenotype of several immune cell populations associated with COVID-19 severity. Our data indicate that intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.
    Keywords covid19
    Language English
    Publishing date 2023-04-26
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.04.24.23288921
    Database COVID19

    Kategorien

  3. Article ; Online: Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction.

    Harm, Tobias / Rath, Dominik / Kreisselmeier, Klaus-Peter / Baas, Livia / Prang, Carolin / Gekeler, Sarah / Schröder, Stephen / Gawaz, Meinrad Paul / Geisler, Tobias / Müller, Iris Irmgard / Müller, Karin Anne Lydia

    Thrombosis research

    2023  Volume 230, Page(s) 45–54

    Abstract: Background: Intracoronary thrombus formation is a main cause of acute myocardial infarction triggered by platelet activation. However, there are no data on the impact of different treatment strategies with antiplatelet agents before percutaneous ... ...

    Abstract Background: Intracoronary thrombus formation is a main cause of acute myocardial infarction triggered by platelet activation. However, there are no data on the impact of different treatment strategies with antiplatelet agents before percutaneous coronary intervention (PCI) on histological characteristics of thrombus formation.
    Objective: In this study, we investigate the impact of preinterventional administration of the P2Y12-inhibitors clopidogrel and prasugrel on thrombus composition, highlighting significant changes associated with the antiplatelet pre-treatment.
    Methods: We prospectively enrolled 104 consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing immediate PCI and thrombus aspiration by immunohistochemical staining along with RNA-sequencing employing Nanostring analysis. Fifty-two patients were treated with either prasugrel loading (60 mg) or clopidogrel loading (600 mg) prior to PCI, respectively.
    Results: In Patients with STEMI, intracoronary thrombus architecture was significantly altered between patients pre-treated with prasugrel when compared to clopidogrel. Fibrin content of thrombi was significantly decreased (41.8 % versus 66.7 %, p = 0.009) after pre-treatment with prasugrel compared to clopidogrel. Furthermore, levels of MPO positive cells in intracoronary thrombi were significantly decreased in patients with prasugrel pre-treatment (90.5 versus 201.1, p = 0.014) indicating an association of antiplatelet pre-treatment and the inflammatory responses during thrombus formation. Most strikingly, we observed significant differences among both pre-treatment groups regarding altered RNA expression and signaling pathways of thrombo-inflammatory processes within the thrombotic material, which were independently associated with antiplatelet strategies.
    Conclusions: Our study elucidates the impact of antiplatelet pre-treatment on thrombus remodeling and architecture, thereby lowering the risk of recurrent adverse cardiovascular events in prasugrel-treated patients.
    MeSH term(s) Humans ; Prasugrel Hydrochloride/pharmacology ; Prasugrel Hydrochloride/therapeutic use ; Clopidogrel/therapeutic use ; ST Elevation Myocardial Infarction/drug therapy ; ST Elevation Myocardial Infarction/etiology ; Percutaneous Coronary Intervention/adverse effects ; Treatment Outcome ; Myocardial Infarction/drug therapy ; Myocardial Infarction/etiology ; Platelet Aggregation Inhibitors/adverse effects ; Thrombosis/etiology ; RNA
    Chemical Substances Prasugrel Hydrochloride (G89JQ59I13) ; Clopidogrel (A74586SNO7) ; Platelet Aggregation Inhibitors ; RNA (63231-63-0)
    Language English
    Publishing date 2023-08-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 121852-9
    ISSN 1879-2472 ; 0049-3848
    ISSN (online) 1879-2472
    ISSN 0049-3848
    DOI 10.1016/j.thromres.2023.08.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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